Trajectories of Cognition in Middle Age: Implications for Alzheimer's Disease and Related Dementias in the U.S.

项目摘要/摘要 美国阿尔茨海默氏症和相关痴呆症(ADRD)的人数预计将达到13.8人 到2050年将达到100万。鉴于目前缺乏针对ADRD的疾病修正治疗，再加上有证据表明 ADRD经过几十年的发展，人们对制定预防战略的兴趣日益浓厚。中年(即， 45岁)被越来越多地认为是一个关键的生命过程时期，以认知上的可改变的风险因素为目标 拒绝和ADRD。先前的研究已经确定了中年的个人水平的风险因素，包括慢性 例如高血压和肥胖症，以及过度饮酒等与健康有关的行为。这个 2020年柳叶刀委员会估计，解决这些中年风险因素可能导致高达15%的 痴呆症被预防或拖延。然而，最近的数据表明，有必要将目光投向个人以外的领域- 研究环境暴露对改善中年健康结果的潜在作用的水平因素 并减轻痴呆症的总体负担。自1990年以来，作为危险因素的慢性病的流行 ADRD在中年人中有所增加，特别是在社会经济地位较低的个人中。 这些趋势的原因尚不完全清楚，但一个主要的假设是，较低的社会保障水平处于中等水平 年龄通过暴露在社会和身体上导致与衰老有关的疾病的过早发作 环境(例如，社会支持水平、犯罪、粮食不安全、污染)。越来越多的研究表明 将这些环境因素与老年人认知能力下降和ADRD的风险联系起来，这些因素可能 也会影响中年的认知轨迹和ADRD的风险。然而，关键的知识差距 留下来。首先，目前尚不清楚中年人的认知结果是否正在恶化，也不清楚环境因素是否会恶化 暴露在空气中会增加中年时认知能力下降的风险。此外，鉴于认知能力下降和 老年人的ADRD是环境和遗传风险因素相互作用的结果，目前还不清楚是如何造成的 遗传风险会导致中年认知能力下降。一项针对中年人的纵向研究 包括环境暴露的衡量标准和解决这些问题所需的基因数据。这个 这项提议的项目的目标是检查中年人的认知结果是否恶化，以及如何 环境和遗传风险因素导致这一年龄段的认知能力下降。具体目标是 目的：(1)研究美国中年人认知障碍的流行病学，包括确定 认知轨迹和“认知损害无痴呆”(CIND)的发生率随时间的变化；(2)决定是否 环境和遗传因素预测认知轨迹和事件CIND；以及(3)复制我们的 第二个数据集中的分析。我们将使用具有全国代表性的纵向数据来实现这些目标 来自NIA资助的健康和退休研究。研究结果将有助于阐明高血压的负担和机制。 在中年时认知能力下降，并为政策规划提供信息，以减轻预计的痴呆症负担。

PROJECT SUMMARY/ABSTRACT The number of Americans with Alzheimer's disease and related dementias (ADRD) is projected to reach 13.8 million by 2050. Given the current lack of disease-modifying treatments for ADRD coupled with evidence that ADRD develops over decades, there is growing interest in developing prevention strategies. Middle age (i.e., 45-64 years) is increasingly recognized as a key life course period to target modifiable risk factors for cognitive decline and ADRD. Prior studies have identified individual-level risk factors in middle age, including chronic conditions such as hypertension and obesity and health-related behaviors such as excessive alcohol use. The 2020 Lancet Commission estimated that addressing these mid-life risk factors could result in up to 15% of dementias being prevented or delayed. However, recent data suggests the need to look beyond individual- level factors to examine the potential role of environmental exposures to improve health outcomes in mid-life and reduce overall dementia burden. Since 1990, the prevalence of chronic conditions that are risk factors for ADRD has increased in middle-aged adults, particularly in individuals with lower socioeconomic status (SES). The reasons for these trends are not yet fully understood, but a leading hypothesis is that lower SES in middle age is leading to premature onset of aging-related conditions through exposures in the social and physical environment (e.g., levels of social support, crime, food insecurity, pollution). A growing number of studies have linked such environmental factors to risk of cognitive decline and ADRD in older adults, and these factors could also be impacting cognitive trajectories and risk of ADRD in middle age. However, key knowledge gaps remain. First, it is unknown if cognitive outcomes are worsening in middle-aged adults, nor if environmental exposures increase the risk of cognitive decline in middle age. Additionally, whereas cognitive decline and ADRD in older adults result from the interplay of environmental and genetic risk factors, it is unclear how genetic risk contributes to cognitive decline in middle age. A longitudinal study of middle-aged adults that includes measures of environmental exposures and genetic data is needed to address these questions. The objective of the proposed project is to examine if cognitive outcomes are worsening in middle age and how environmental and genetic risk factors contribute to cognitive decline in this age group. The specific aims are to: (1) examine the epidemiology of cognitive impairment in middle-aged adults in the U.S., including identifying cognitive trajectories and incidence of “cognitive impairment no dementia” (CIND) over time; (2) determine if environmental and genetic factors predict cognitive trajectories and incident CIND; and (3) replicate our analyses in a second dataset. We will complete these aims using longitudinal nationally representative data from the NIA-funded Health and Retirement Study. Findings will help elucidate the burden and mechanisms of cognitive decline in middle age and inform policy planning to mitigate the projected burden of dementia.